NM_000070.3:c.327_328dupCC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong
The NM_000070.3(CAPN3):c.327_328dupCC(p.Arg110ProfsTer18) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000513 in 1,461,420 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
CAPN3
NM_000070.3 frameshift
NM_000070.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.91
Publications
1 publications found
Genes affected
CAPN3 (HGNC:1480): (calpain 3) Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed. [provided by RefSeq, Jul 2008]
CAPN3 Gene-Disease associations (from GenCC):
- muscular dystrophy, limb-girdle, autosomal dominantInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- autosomal recessive limb-girdle muscular dystrophyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- autosomal recessive limb-girdle muscular dystrophy type 2AInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae)
- limb-girdle muscular dystrophyInheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
- muscular dystrophy, limb-girdle, autosomal dominant 4Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 16 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PP5
Variant 15-42384497-T-TCC is Pathogenic according to our data. Variant chr15-42384497-T-TCC is described in ClinVar as Pathogenic. ClinVar VariationId is 210563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000070.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CAPN3 | NM_000070.3 | MANE Select | c.327_328dupCC | p.Arg110ProfsTer18 | frameshift | Exon 2 of 24 | NP_000061.1 | P20807-1 | |
| CAPN3 | NM_024344.2 | c.327_328dupCC | p.Arg110ProfsTer18 | frameshift | Exon 2 of 23 | NP_077320.1 | P20807-3 | ||
| CAPN3 | NM_173087.2 | c.327_328dupCC | p.Arg110ProfsTer18 | frameshift | Exon 2 of 21 | NP_775110.1 | P20807-2 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CAPN3 | ENST00000397163.8 | TSL:1 MANE Select | c.327_328dupCC | p.Arg110ProfsTer18 | frameshift | Exon 2 of 24 | ENSP00000380349.3 | P20807-1 | |
| CAPN3 | ENST00000357568.8 | TSL:1 | c.327_328dupCC | p.Arg110ProfsTer18 | frameshift | Exon 2 of 23 | ENSP00000350181.3 | P20807-3 | |
| CAPN3 | ENST00000349748.8 | TSL:1 | c.327_328dupCC | p.Arg110ProfsTer18 | frameshift | Exon 2 of 21 | ENSP00000183936.4 | P20807-2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461420Hom.: 0 Cov.: 30 AF XY: 0.0000426 AC XY: 31AN XY: 727052 show subpopulations
GnomAD4 exome
AF:
AC:
75
AN:
1461420
Hom.:
Cov.:
30
AF XY:
AC XY:
31
AN XY:
727052
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33474
American (AMR)
AF:
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53392
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
74
AN:
1111598
Other (OTH)
AF:
AC:
0
AN:
60384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
4
8
12
16
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0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
3
-
-
Autosomal recessive limb-girdle muscular dystrophy type 2A (3)
3
-
-
not provided (3)
1
-
-
Muscular dystrophy, limb-girdle, autosomal dominant 4 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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